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Downregulation of ATM Gene and Protein Expression in Canine Mammary Tumors
T M M Raposo-Ferreira1, R C Bueno2, E M Terra1
1Department of Veterinary Clinic and Surgery, UNESP, Jaboticabal, São Paulo, Brazil.
Abstract:
The ataxia telangiectasia mutated (ATM) gene encodes a protein associated with DNA damage repair and maintenance of genomic integrity. In women, ATM transcript and protein downregulation have been reported in sporadic breast carcinomas, and the absence of ATM protein expression has been associated with poor prognosis. The aim of this study was to evaluate ATM gene and protein expression in canine mammary tumors and their association with clinical outcome. ATM gene and protein expression was evaluated by reverse transcription-quantitative polymerase chain reaction and immunohistochemistry, respectively, in normal mammary gland samples (n = 10), benign mammary tumors (n = 11), nonmetastatic mammary carcinomas (n = 19), and metastatic mammary carcinomas (n = 11). Lower ATM transcript levels were detected in benign mammary tumors and carcinomas compared with normal mammary glands (P = .011). Similarly, lower ATM protein expression was observed in benign tumors (P = .0003), nonmetastatic mammary carcinomas (P < .0001), and the primary sites of metastatic carcinomas (P < .0001) compared with normal mammary glands. No significant differences in ATM gene or protein levels were detected among benign tumors and nonmetastatic and metastatic mammary carcinomas (P > .05). The levels of ATM gene or protein expression were not significantly associated with clinical and pathological features or with survival. Similar to human breast cancer, the data in this study suggest that ATM gene and protein downregulation is involved in canine mammary gland tumorigenesis.
Insights
Ataxia telangiectasia mutated (ATM) gene and protein are downregulated in canine mammary tumors. This suggests ATM
Area of Science:
- Veterinary Oncology
- Molecular Biology
- Genetics
Background:
- The ataxia telangiectasia mutated (ATM) gene is crucial for DNA repair and genomic stability.
- ATM downregulation and absence of its protein expression are linked to poor prognosis in human breast cancer.
- ATM's role in canine mammary tumors remains largely unexplored.
Purpose of the Study:
- To investigate ATM gene and protein expression in canine mammary tumors.
- To determine the association between ATM expression and clinical outcomes in dogs with mammary tumors.
Main Methods:
- Quantitative analysis of ATM gene expression using reverse transcription-quantitative polymerase chain reaction.
- Immunohistochemistry to evaluate ATM protein expression.
- Comparison of ATM levels in normal mammary glands, benign tumors, and nonmetastatic/metastatic carcinomas.
Main Results:
- Lower ATM transcript levels were observed in benign mammary tumors and carcinomas compared to normal mammary glands.
- ATM protein expression was significantly reduced in benign tumors and all grades of mammary carcinomas versus normal tissue.
- No significant differences in ATM gene or protein levels were found among benign, nonmetastatic, and metastatic mammary carcinomas.
- ATM expression levels did not correlate with clinical-pathological features or survival outcomes.
Conclusions:
- ATM gene and protein downregulation occurs during canine mammary gland tumorigenesis.
- Similar to human breast cancer, ATM alterations are implicated in the development of canine mammary tumors.
- Further research is needed to understand the precise role of ATM in canine mammary tumor progression and prognosis.
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